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Abstract

Background Radiofrequency catheter modification of AV conduction can be used to control the ventricular rate during atrial fibrillation both in the baseline state and during exercise. Slow-pathway ablation has been suggested to be the mechanism for this response. The purpose of this study was to determine the effect of slow-pathway ablation on the ventricular rate in atrial fibrillation during autonomic blockade and sympathetic stimulation in patients with AV nodal reentrant tachycardia (AVNRT).

The ventricular rate during atrial fibrillation has been found to be reduced significantly both at rest and during exercise after radiofrequency modification of AV conduction.123 Previous studies have suggested that the mechanism responsible for controlling the ventricular rate during atrial fibrillation is slow-pathway ablation.2345 However, these prior studies investigated the effects of slow-pathway ablation in the resting state or during autonomic blockade, neither of which may accurately reflect the findings during states of sympathetic stimulation.45 Therefore, the purpose of this study was to determine the effect of slow-pathway ablation on ventricular rate during atrial fibrillation in the presence of autonomic blockade and β-adrenergic stimulation.

Methods

Patient Population

This study consisted of 35 patients who had typical AV nodal reentrant tachycardia (AVNRT) that was reproducibly inducible in the baseline state during electrophysiological testing and who underwent radiofrequency ablation of the slow pathway. The group was made up of 26 women and 9 men with a mean age of 48±13 years (±SD). No patient had structural heart disease. These patients had been treated with a mean of 1.4±0.9 antiarrhythmic medications because of symptoms caused by paroxysmal supraventricular tachycardia for a mean of 16±11 years before the ablation procedure.

Electrophysiological Testing

The investigational protocol was approved by the Committee for Human Research at the University of Michigan. Informed consent was obtained from the patients, and the electrophysiological procedures were performed with patients in the fasting state after all antiarrhythmic medications had been discontinued for at least five half-lives. Three 7F quadripolar electrode catheters were inserted into the right femoral vein and positioned in the high right atrium, across the tricuspid valve to record the His bundle electrogram, and in the right ventricle. The catheter across the tricuspid valve had a 4-mm distal electrode and a deflectable tip (Mansfield EP) and was used for ablation. Leads V1, VII, and VIII and the intracardiac electrograms were displayed on an oscilloscope and recorded on a Mingograph 7 recorder (Siemens-Elema). Pacing was performed with a programmable stimulator (Bloom Associates).

The initial portion of the electrophysiology procedure was directed at determining the presence of dual AV nodal physiology, measuring the conduction properties and refractory periods of the fast and slow AV nodal pathways, and determining that the mechanism of the paroxysmal supraventricular tachycardia was typical AVNRT.6 Programmed stimulation and incremental pacing were performed in the right atrium and ventricle to define the anterograde and retrograde conduction and refractoriness of the AV node and to confirm that typical AVNRT could be reproducibly provoked.

Catheter Ablation Protocol

Radiofrequency energy was delivered by a generator that supplied a continuous unmodulated sine wave output at a frequency of 500 kHz. Mapping was performed in the posteroseptal right atrium, in the region of the coronary sinus. Suitable target sites for slow-pathway ablation were identified during sinus rhythm. Target sites were identified by an AV electrogram ratio <0.5 and by the presence of a multicomponent atrial electrogram.78 After a target site was identified, radiofrequency current was applied at 32 W for 10 to 60 seconds. The inducibility of AVNRT was assessed after each application of radiofrequency energy. In each patient, AVNRT was successfully eliminated. Induction of a single AV nodal echo by programmed stimulation in the baseline state and during the infusion of isoproterenol was considered an acceptable end point for the ablation procedure.9

The presence or absence of residual slow-pathway function was noted after successful ablation of AVNRT. The criteria for residual slow-pathway function consisted of dual AV nodal physiology and/or AV nodal echo beats after elimination of inducible AVNRT. AV nodal echo beats were defined as echo beats that had a concentric atrial activation sequence and occurred in association with prolongation of the AH interval, were reproducible, and occurred simultaneously with a QRS complex with a fixed VA relationship. Among the 13 patients assigned to autonomic blockade, residual slow-pathway function was present after slow-pathway ablation in only 1 patient. Among the 21 patients who received isoproterenol, 5 had residual slow-pathway function.

Study Protocol

To eliminate the possible confounding effects of changes in sympathetic or vagal tone, the study protocol was performed in 14 patients during autonomic blockade. Autonomic blockade was achieved with 0.04 mg/kg IV atropine and 0.2 mg/kg IV propranolol administered over 5 minutes.10 The initial doses of propranolol and atropine were 14.8±5.8 and 3.1±1.2 mg, respectively. To evaluate the effects of sympathetic stimulation, 21 other patients underwent the study protocol during the intravenous infusion of 2 μg/min of isoproterenol. Five minutes after administration of the drugs for autonomic blockade or when the steady-state effect of isoproterenol on the heart rate had been reached, atrial and ventricular incremental and programmed simulation was performed to define anterograde and retrograde AV node conduction and refractoriness. Atrial fibrillation was then induced by rapid atrial pacing at cycle lengths of 150 to 200 ms. The minimum duration of atrial fibrillation required for analysis was 15 seconds. The mean duration of atrial fibrillation used for analysis before and after ablation was 34.4±19.5 and 29.4±19.8 seconds (P=.4), respectively. The mean cycle length of the ventricular response and the minimum and maximum cycle lengths were determined. After successful catheter ablation, atropine and propranolol were administered to patients assigned to autonomic blockade in doses sufficient to achieve a sinus cycle length within 20 ms of the preablation sinus cycle length. After the ablation procedure, there was only one patient in whom the sinus cycle length was not within 20 ms of the preablation cycle length, and this patient received an additional 13.6 mg propranolol and 2.7 mg atropine. In the remaining 13 patients, the sinus cycle length was within 20 ms of the preablation sinus cycle length, and additional drug administration was not necessary. Isoproterenol was administered as described above in patients assigned to sympathetic stimulation. Electrophysiological testing and induction of atrial fibrillation were repeated after the ablation procedure.

Statistical Analysis

Continuous variables are expressed as mean±SD and were compared by use of a paired or unpaired t test when appropriate. Nominal variables were compared by χ2 analysis. Probability values <.05 were considered statistically significant.

Results

Autonomic Blockade

After elimination of AVNRT with the slow-pathway approach, the mean ventricular cycle length during atrial fibrillation in the setting of autonomic blockade in 14 patients was prolonged from 448±34 to 525±103 ms (P<.01; Fig 1⇓). The maximum ventricular cycle length (640±105 versus 798±226 ms, P=.04) during atrial fibrillation also was prolonged significantly after successful slow-pathway ablation. However, the minimum ventricular cycle length (361±42 versus 403±83 ms, P=.06) was not significantly affected by slow-pathway ablation.

Mean ventricular cycle length (CL) during atrial fibrillation in the setting of autonomic blockade before and after slow-pathway ablation.

The fast-pathway effective refractory period was 280±56 ms before ablation and 269±44 ms (P=.04) after ablation. The slow-pathway refractory period before ablation was 240±25 ms. Residual slow-pathway function was present in only one patient after ablation, and the slow-pathway effective refractory period was 260 ms. The postablation AV block cycle length (364±58 ms) did not change significantly from the preablation value (342±49 ms, P=.06). The mean preablation ventricular cycle length during atrial fibrillation correlated with the fast-pathway refractory period (r=.7, P<.01), the slow-pathway refractory period (r=.7, P=.03), and the shortest cycle length associated with 1:1 conduction during atrial pacing (r=.8, P=.001). After ablation, the mean ventricular cycle length during atrial fibrillation correlated with the shortest cycle length associated with 1:1 conduction during atrial pacing (r=.7, P<.01) but not with the postablation fast-pathway refractory period.

Mean ventricular cycle length (CL) during atrial fibrillation in the setting of sympathetic stimulation before and after slow-pathway ablation.

Before ablation, the fast-pathway effective refractory period, slow-pathway effective refractory period, and shortest cycle length associated with 1:1 conduction during atrial pacing were 227±26, 200±7, and 254±38 ms, respectively. After ablation, the fast-pathway refractory period (223±27 ms, P=.6), slow-pathway effective refractory period (210±17 ms, P=.3), and shortest cycle length associated with 1:1 conduction during atrial pacing (265±39 ms, P=.2) did not change significantly from preablation values. The fast-pathway effective refractory period in the five patients with residual slow-pathway function (236±21 ms) did not change significantly from the preablation value (244±27 ms, P=.1). Likewise, when residual slow-pathway function was not present after ablation, the fast-pathway effective refractory period (221±25 ms) did not change significantly from the preablation value (223±23 ms, P=.1). Before ablation, the mean ventricular cycle length during atrial fibrillation correlated with the fast-pathway (r=.6, P<.01) and slow-pathway (r=.7, P=.03) refractory periods but not with the shortest cycle length associated with 1:1 conduction during atrial pacing (P=.2). After ablation, the effective refractory period of the fast pathway (r=.5, P=.03) but not the slow pathway (P=.2) correlated with the postablation ventricular cycle length during atrial fibrillation. The shortest cycle length associated with 1:1 conduction during atrial pacing after ablation correlated with the mean ventricular cycle length during atrial fibrillation (r=.7, P=.001).

Discussion

Major Findings

The results of this study demonstrate that the ventricular rate during atrial fibrillation after slow-pathway ablation slows in the setting of autonomic blockade but not during β-adrenergic stimulation. Therefore, although slow-pathway ablation may account for slowing of the ventricular rate in the resting state or during autonomic blockade after radiofrequency modification of AV conduction, it cannot explain the slowing of the ventricular rate observed during states of β-adrenergic stimulation, such as exercise.

Comparison With Previous Studies

Two prior studies investigated the effect of slow-pathway ablation on ventricular rate during atrial fibrillation.45 Both studies demonstrated slowing of the ventricular rate during atrial fibrillation after slow-pathway ablation. Blanck et al4 demonstrated this during autonomic blockade, whereas Tebbenjohanns and colleagues5 performed their study without pharmacological intervention. In these studies, the mean ventricular cycle length during atrial fibrillation was prolonged by 16% and 24%, respectively. However, neither study examined the effects of sympathetic stimulation. The present study found prolongation of the ventricular cycle length with autonomic blockade by a similar percentage (17%), but this is the only report to date to demonstrate the influence of sympathetic stimulation during atrial fibrillation after slow-pathway ablation. Because modification of AV conduction effectively slows the ventricular response during exercise and isoproterenol administration,1 administration of isoproterenol is important to include in any study designed to determine the mechanism responsible for the efficacy of this procedure.

Electrophysiological Effects

The fast-pathway effective refractory period has been noted to paradoxically shorten after successful slow-pathway ablation.1112 The mechanism responsible for this phenomenon may be the removal of electrotonic effects on the fast pathway after the slow pathway is destroyed.41314 The results of the present study in the setting of autonomic blockade confirm the results of these prior studies. During isoproterenol infusion, the fast-pathway effective refractory period was shortened by 17% compared with that during autonomic blockade. However, during sympathetic stimulation, the fast-pathway effective refractory period did not shorten any further after slow-pathway ablation. These results suggest that any possible electronic inhibition of the fast pathway by the slow pathway is eliminated in the setting of sympathetic stimulation.

The data presented here suggest that the AV node effective refractory periods and the shortest cycle length associated with 1:1 conduction during atrial pacing correlate with the mean atrial fibrillation cycle length before and after slow-pathway ablation. These results confirm the results of a previous study that demonstrated that the conductivity and refractory period of the AV node correlate with the ventricular rate during atrial fibrillation.15

Possible Mechanisms

Two mechanisms have been proposed to account for the therapeutic slowing of the ventricular rate during atrial fibrillation by radiofrequency catheter modification of AV conduction: slow-pathway ablation2345 and partial ablation of the compact AV node.1

The data presented here and in previous reports demonstrate that the slow-pathway approach to ablation of AVNRT results in slowing of the ventricular response to atrial fibrillation in the setting of autonomic blockade.45 The results of the present study, however, demonstrate no effect of slow-pathway ablation on the ventricular rate during atrial fibrillation during isoproterenol administration. In contrast, radiofrequency catheter modification of AV conduction results in slowing of the ventricular rate during atrial fibrillation even during sympathetic stimulation.123 These results suggest that during rest or autonomic blockade, the predominant input to the AV node is through the slow pathway. Therefore, ablation of the slow pathway may result in slowing of the ventricular rate during atrial fibrillation. However, during sympathetic stimulation, the fast pathway may be activated so that slow-pathway ablation no longer affects the ventricular rate during atrial fibrillation. Prior studies demonstrated that the fast pathway often conducts slowly in the baseline state but rapidly during sympathetic stimulation.1617181920 In these reports, VA conduction was absent or sluggish in the baseline state, but rapid retrograde conduction and inducible AVNRT became manifest during isoproterenol administration.1617181920 A similar phenomenon would explain why slow-pathway ablation in the present study affected the ventricular rate in atrial fibrillation during autonomic blockade but not during isoproterenol administration.

Study Limitations

A possible limitation of this study is that some patients had relatively brief episodes of inducible atrial fibrillation. A previous study suggested that the mean ventricular rate during atrial fibrillation may be estimated accurately with a 20-second sample of atrial fibrillation, whereas a 120-second sample is required to estimate the minimum ventricular rate.21 In the present study, the minimum duration of atrial fibrillation used for analysis was 15 seconds (mean, ≈30 seconds). Therefore, errors in the mean ventricular cycle length resulting from inadequate sample duration probably were minimal.

Conclusions

In conclusion, the results of this study demonstrate that although slow-pathway ablation of the AV node results in a slowing of the ventricular rate during atrial fibrillation in the setting of autonomic blockade, there is no slowing of the ventricular rate during sympathetic stimulation. Therefore, the therapeutic response to radiofrequency modification of AV conduction to control the ventricular rate during atrial fibrillation, which is manifest under all conditions of autonomic tone,123 cannot be explained by slow-pathway ablation. This conclusion is different from the conclusions of previous studies that examined the effects of slow-pathway ablation on ventricular rate during atrial fibrillation, and this difference can be explained by the failure of other studies to determine the effects of sympathetic stimulation.45 These findings imply that the anterior inputs to the AV node are sufficient to manifest a rapid rate during atrial fibrillation even after ablation of the posterior inputs to the AV node. Therefore, it is likely that the therapeutic effects of radiofrequency modification of AV conduction to control the ventricular rate during atrial fibrillation are explained at least in part by injury to the AV node itself.